FDA Approves Trastuzumab Biosimilar

The FDA has approved the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst), which now has has approved indications for HER2-positive patients with breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

The FDA has approved the trastuzumab (Herceptin) biosimilar MYL-1401O (Ogivri; trastuzumab-dkst), which is co-developed by Mylan and Biocon.

MYL-1401O has approved indications for HER2-positive patients with breast cancer or metastatic gastric or gastroesophageal junction adenocarcinoma, the same indications as trastuzumab. Genentech, the manufacturer of trastuzumab, holds an exclusive license for the metastatic gastric cancer indication. The companies cannot market the drug for that purpose until the exclusive license expires.

“The FDA continues to grow the number of biosimilar approvals, helping to promote competition that can lower health care costs. This is especially important when it comes to diseases like cancer, that have a high cost burden for patients,” FDA Commissioner Scott Gottlieb, MD, said in a press release. “We’re committed to taking new policy steps to advance our biosimilar pathway and promote more competition for biological drugs.”

Mylan and Biocon submitted a biologics license application (BLA) to the FDA for MYL-1401O in November 2016, and the agency had set an action deadline of September 3, 2017. In July 2017, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 16-0 to recommend approval of MYL-1401O. However, on August 30, the FDA announced that it had extended its decision deadline on the BLA by 3 months.

The BLA includes phase III results from HERiTAge, a 2-part, multicenter, double-blind, randomized, parallel-group study. Patients with measurable HER2-positive metastatic breast cancer who had not received prior chemotherapy or trastuzumab for metastatic disease were randomly assigned to MYL-1401O (n =230) or trastuzumab with docetaxel or paclitaxel (n = 228).

Patients underwent a minimum of 8 cycles in Part 1 of the trial, with trastuzumab continuing until progression. Both forms of trastuzumab were administered with a loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg every 3 weeks.

In Part 2, patients who had stable disease or better could continue with MYL-1401O or trastuzumab. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival, overall survival, time to progression, safety, and tolerability.

MYL-1401O demonstrated an ORR after 24 weeks of 69.6% among women who received the biosimilar in combination with a taxane compared with a 64% ORR for patients who took trastuzumab plus a taxane. The ratio of ORR for MYL-1401O to trastuzumab was 1.09—both 90% CI (0.974-1.211) and 95% CI (0.954-1.237). The difference in ORR between the 2 arms was 6.0% (90% CI, -1.3%-13.2%). At the week 48 cutoff, the median duration of response was 9.7 months in both groups.

In the per protocol population, ORR was 70% for MYL-1401O compared with 67% for trastuzumab. The ratio of ORR was 1.06 (90% CI, 0.96-1.18).

Progression-free survival was nearly identical between the 2 groups (stratified HR, 0.95; 95% CI, 0.71-1.25). Median overall survival had not been met in either group.

Safety data also were comparable. Serious adverse events (AEs) occurred in 39.3% of the patients in the MYL-1401O arm compared with 37.0% in the trastuzumab arm, with neutropenia as the most frequently reported serious AE in both arms (57.5% vs 54.1%, respectively).

The BLA also included 2 nonclinical animal studies: a single-dose comparative pharmacokinetic study in cynomolgus monkeys comparing MYL-1401O to EU-trastuzumab, and a 4-week, repeat-dose toxicity and toxicokinetic study in cynomolgus monkeys comparing MYL-14010 to EU-trastuzumab.

Additional data were provided from the single-dose, randomized, double-blind comparative MYL-HER-1002 pharmacokinetic study. In the study, 120 healthy male subjects were given an 8 mg/kg infusion of MYL-1401O (n = 42), US-approved trastuzumab (n = 37), or EU-approved trastuzumab (n = 41). The predefined PK endpoints were AUC0-∞, AUC0-t, and CMax.


In a briefing document used for the July ODAC meeting, FDA staff concluded that data from MYL-HER-1002 showed that MYL-1401O demonstrated a similar PK profile with US- and EU-approved trastuzumab (see table).